Methoxatin (pyrroloquinoline quinone or PQQ) is a coenzyme for various oxidoreductases, including alcohol dehydrogenase, aldehyde dehydrogenase and D-glucose dehydrogenase. (Ameyama et al., Anal. Biochem., 151, 263-7 (1985)). Methoxatin was originally discovered in bacteria (Hauge, J. Biol. Chem., 239, 3630-9 (1964); Anthony et al., Biochem. J., 104, 960-9 (1967); Salisbury et al., Nature, 280, 843-4 (1979); and Westerling et al., Biochem Biophys Res Commun, 87, 719-24 (1979)). Methoxatin was later determined to have a nutritional role in mammals (Killgore et al., Science, 245, 850-2 (1989); and Kasahara et al., Nature, 422, 832 (2003)) and to exhibit a growth role in plants. (Choi et al., Plant Physiology 146: 657-668 (2008)). Those proteins that bind methoxatin as a coenzyme are also known as quinoproteins.
The widespread occurrence of methoxatin in nature led to exploration of its chemistry. Methods for synthesizing methoxatin have been published (see e.g., Martin et al., Helv. Chim. Acta, 76, 1667-73 (1993); Hendrickson et al., J. Org. Chem., 50, 1688-95 (1985); Corey et al., J. Am. Chem. Soc., 103, 5599-5600 (1981); and Itoh et al., Natural Product Rep., 45-53 (1995)). The synthesis of solid-supported derivatives of methoxatin has been reported. (Zayats et al., Electroanalysis, 20, 583-601 (2008); US2003/0148169; US2004/0245101; US2005/0130248; and US2006/0269826). PQQ co-factor-macromolecule conjugates that have been used in enzyme-amplified detection and diagnostic applications (US2006/0199187 and US2006/0199241).
There is a need in the art for additional methoxatin derivatives which can be used in diagnostic and biological applications.